The Clinical Research in ALS and related disorders for Therapy Development (CREATE) RDCRC will focus on ALS and a group of related degenerative disorders that includes PLS, HSP, PMA, and FTD. This group of disorders is unified by their degenerative nature; their overlapping phenotypes resulting from degeneration of upper motor neuron, lower motor neuron and frontotemporal neuronal systems; their overlapping genetic susceptibility; their shared underlying biology; and their uniform lack of effective therapies. These disorders also share common challenges with respect to biomarker and therapeutic development - challenges that might be overcome through a shared experimental approach. The over-arching goals of the CREATE RDCRC are to better understand the relationship between genotype and phenotype for this group of disorders, and to develop disease biomarkers with a view to facilitating drug discovery and therapeutic development for patients afflicted with one of these neurodegenerative disorders. The CREATE RDCRC brings together a multi-disciplinary group of investigators and a diverse array of patient advocacy groups representing the patient populations that are the focus of our research efforts. These include the ALS Association, the Muscular Dystrophy Association, the Spastic Paraplegia Foundation, the Association for Frontotemporal Degeneration, the ALS Recovery Fund and PatientsLikeMe. The diversity of expertise within the CREATE RDCRC spans clinical neurology (neuromuscular disease and cognitive/behavioral neurology), genetics, genetic epidemiology, molecular neuroscience, biomarker development, drug discovery, biostatistics, and clinical trials, as well as patient advocacy, education and outreach. The CREATE Consortium, therefore, is a truly translational enterprise that effectively bridges the gap between basic scientists and investigators engaged in applied clinical research. Our new collaboration with the Ontario Brain Institute Neurodegenerative Disease Research Initiative, and the European STRENGTH Consortium significantly enhance the potential impact of this RDCRC.